In order to regenerate non-containing bony defects by bone formation, such as e.g. in horizontal or vertical augmentations in the maxilla or mandible, mechanical stabilization of the defect is required (Bendkowski 2005 “Space to Grow” The Dentist: 3; Merli, Migani et al. 2007 Int. J. Oral Maxillofac. Implants 22(3): 373-82; Burger 2010 J. Oral Maxillofac. Surg. 68(7): 1656-61; Louis 2010 Oral Maxillofac. Surg. Clin. North Am. 22(3): 353-68). Indeed, oral tissues are exposed to complex mechanical forces during mastication, swallowing, tongue movement, speech, tooth movement and orthodontic treatment. Especially during wound healing following surgical procedures, internal and external forces may occur, creating pressure, shear forces and bending moments upon. the regenerative device and newly formed tissue.
A form stable rnembrane resisting those forces is a useful means for bringing that mechanical stabilization.
It is known to use for that purpose Ti-meshes, Ti-plates or Ti-reinforced PTFE form stable membranes which have to be removed after bone regeneration during a second surgery. An example of a commercially available Ti-reinforced form stable membrane is the Cytoplast® membrane marketed by Osteogenies. However, the occurrence of dehiscences or other complications when using expanded Ti-reinforced membranes is reported to be high (Strietzel 2001 Mund Kiefer Gesichtschir. 5(1): 28-32; Merli, Migani et al. 2007 supra; Rocchietta, Fontana et al. 2008 J. Clin. Periodontol. 35(8 Suppl): 203-15).
Non reinforced PTFE membranes werewidely used prior the introduction of resorbable collagen membranes in 1996, but disappeared very fast after the introduction of collagen membranes.
To avoid the need of removal of a form stable membrane or meshes in a second surgery, a resorbable form stable membrane is of interest. Several resorbable form stable membranes or meshes have been described, essentially made from PLA (poly-lactic acid) or PLGA (poly-lactic-co-glycolic acid). Examples are notably (1) “Sonic Weld RX®” and “Resorb-X®” from KLS Martin, (2) “Guidor®” from Sunstar Americas, (3) the “Inion GTR System™” from Curasan and (4) “RapidSorb®” from Depuy Synthes. The disadvantage of those membranes is that during their in vivo hydrolytic degradation they release lactic and/or glycolic acid which cause tissue irritation and histological signs of a disturbed wound healing (Counts Whitman et al. 1998 Biomed. Mater. Res. 42(2): 303-11; Heinze 2004 Business briefing: Lobal Surgery: 4; Pilling, Mai et al. 2007 Br J. Oral Maxillofac. Surg. 45(6): 447-50).
To overcome PLGA/PLA associated wound healing problems, the use of autologous bone blocks from the patient and partly or completely purified bone blocks, such as e.g. Geistlich Bio-Oss® Block (Geistlich Pharma A.G.) or Puros® Allograft Block (RTI Surgical Inc.), is widely accepted. Autologous bone blocks have the disadvantage that they are harvested from a second site leading to more pain. (Esposito, Grusovin et al. 2009 Eur. J Oral Implantol. 2(3): 167-84)
To enable the use of autologous bone chips harvested during surgery, usually in combination with xenogenic bone graft particles, the so called bone shield technique was developed using autologous cortical bone from the mandibula (Khoury, Hadi et all. 2007 “Bone Augmentation in Oral Implantology”, London, Quintessence). Disadvantages of this procedure are that it is extremely technique sensitive and that it is associated with second site morbidity and more pain. Further, bone shields are applied only laterally, therefore no mechanical protection is given from the coronal aspect of the defect. The term “bone shield” was used for advertising PLA/PLGA membranes as well as a partially demineralized cortical bone shield (Semi-Soft and Soft Lamina Osteobiol® from Tecnoss). The disadvantages of this demineralized bone shield are that bent bone shields have to be fixed always, that they are relatively thick compared to e.g. Ti-reinforced PTFE membranes and that they come only in round shapes with curved edges on the coronal aspect of the bony defect. For dentists, a 6-8 mm wide plateau in the coronal aspect of the ridge would be much more preferred (Wang and Al-Shammari 2002 Int. J. Periodontics Restorative Dent. 22(4): 335-43).
An attempt to combine uneventful healing and form stability is the resorbable form stable collagen membrane disclosed in U.S. Pat. No. 8,353,967-B2, which is prepared from a collagen suspension in 5-25% ethanol/water in a mould by freeze-drying and heating at 100 to 140° C. Such a membrane is manufactured by Osseous Technologies of America and marketed under the trade name “Zimmer CurV Preshaped Collagen Membrane” by Zimmer. That commercial membrane has weak form stability and a thickness of about 1.5 mm rising after incubation in saline to around about 2.3 mm; this may lead to a risk of a high dehiscence rate.
In summary the current solutions for are thus not fully satisfying for dentists or patients. Either a second surgery is necessary and/or there is a high risk of eventful wound healing. Solutions which are not associated with a high risk of eventful wound healing are either not form stable membranes, require a second surgery or have other disadvantages.
US 2013/0197662 discloses a process for fabricating a biomaterial comprising a) joining a porous collagen-based material with a non-porous collagen-based material by applying a controlled amount of a gel comprising collagen to a bonding surface of the non-porous collagen-based material, and contacting a surface of the porous collagen-based material with the gel applied to the bonding surface to partially hydrate a section of the porous material at the interface between materials; b) drying the gel to bond the materials together; and c) crosslinking the collagens in the bonding layers. The fabricated biomaterial obtained combines a porous collagen based material, which may be mineralized [0042], [0048], and a mechanically strong non-porous collagen-based material, thus providing a scaffold for regeneration of load--bearing tissues (notably meniscus, articular cartilage, tendons and ligaments), which has both porosity and mechanical strength, i.e. is able to resist compressional and tensional forces. Nothing is disclosed on the resistance to bending moments of that combined biomaterial or on the composition of the mineralized porous collagen-based material.
US 2014/0193477 teaches that in the fabrication of collagen mats from soluble collagen stretching the collagen prior to its crosslinking increases its mechanical strength, in particular the ultimate tensile strength (UTS), stiffness and elastic modulus (Young's modulus) (see in particular [0109], [0110]).
Langdon, Shari E et al., Biomaterials 1998, 20(2),137-153 CODEN and Chachra, Debbie et al., Biomaterials 1996, 17(19), 1865-1875 CODEN, disclose that stretching a pericardium derived membrane prior to its crosslinking increases its tensile strength and stiffness.